The invention is directed to a matrix for the therapeutic repair of bone and cartilage tissue, methods of producing such a matrix, and methods of using the matrix to grow bone or cartilage. The use of the matrix is accomplished without utilization of ex vivo cultivation methods.
There is a clinical demand for a bone grafting matrix that offers osteoconductive properties equal to autogenous bone and that can be produced in unlimited supply. Although some bone substitutes are available, many consist of materials that have poor physical handling and resorption characteristics that complicate their use and radiographic evaluation.
Similarly, there is no commercially useful or consistently effective product that supports the maintenance of the chondrocyte phenotype of cartilage tissue, despite years of extensive research. Prior strategies to facilitate the repair of damaged cartilage have included the transplantation of existing host cartilage and/or the implantation of prosthetic devices. Limitations of these methods are the availability of donor tissue and the limited lifespan of prosthetic implants. More recently, the ex vivo cultivation of mature chondrocytes on polymeric scaffolds has been used in an attempt to generate cartilage graft material but this has not yet been widely accepted in part because it involves two surgical procedures: one to harvest chondrocytes and the second to implant them after expansion in vitro.
Collagens and glycosaminoglycans are two classes of biomaterials suited for use in bone regeneration. Collagen-based scaffolds have been used in bone grafting. Type I collagen has good cell adhesive properties, in particular, for bone-forming osteoblast cells. In addition, if desired, the inherent cell adhesion sites can be masked to support increased cell-to-cell interaction and adhesion by the incorporation of non cell-adhesive polymers or polysaccharides. Thus, collagen has the capacity to serve both as an active or inert scaffold material for growth.
Hyaluronic acid is a natural component of the cartilage extracellular matrix, and it is readily sterilized, is biodegradable and can be produced in a wide range of consistencies and formats. It is generally biocompatible and its resorption characteristics can be controlled by the manipulation of monomers to polymer forms, most commonly through the esterification of the carboxylic groups of the glucuronic acid residues.
Dextran sulfate is a glycoaminoglycan-like polyionic derivative of dextran and has been shown to be useful as a biomaterial and drug for treatment of hyperlipidemia. It is produced by esterification of dextran, a hydrophilic polymer of glucose synthesized by certain strains of bacteria.
While these materials have been used separately or in combination with other materials, there has been to date no recognition of combinations and methods of making combinations of such materials to form an advantageous matrix for bone and cartilage repair which does not utilize extraneous cross-linking or ionic binding agents.